tbuckley/cabot-search huggingface dataset:
Decorin promotes decidual M1-like macrophage polarization via mitochondrial dysfunction resulting in recurrent pregnancy loss
Authors: Liling Wang, Huan Wang, Jing Luo, Ting Xie, Gil Mor, Aihua Liao
Journal: Theranostics (2022)

Rationale: Recurrent pregnancy loss (RPL) is a distressing disorder that seriously affects the physical and psychological health of women.RPL is also a sentinel risk marker for future obstetric complications and warrants in-depth investigation.Abnormal polarization and functions of decidual macrophages are associated with RPL; however, the underlying mechanisms remain poorly understood.Methods: Decorin expression, localization, and content in the decidua of women with normal pregnancy (NP) and those with RPL were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting, immunofluorescence, and enzyme-linked immunosorbent assay.The profiles of decidual macrophage subsets were determined using flow cytometry and immunofluorescence in both groups.The correlation between decorin content and the proportion of decidual macrophage subsets in the decidua of early NP women was determined using Pearson analysis.The effects of decorin on the polarization and functions of macrophages were assessed in an in-vitro model of Raw264.7 cells via flow cytometry, western blotting, and RT-qPCR.Moreover, the mitochondrial metabolism in Raw264.7 cells under decorin administration was measured via flow cytometry, western blotting, and immunofluorescence.Thirty-three pregnant mice were included in the in vivo model and underwent different treatments.The embryo abortion rate, macrophage phenotype in the spleen and uteri, and placental development were evaluated using flow cytometry and hematoxylin-eosin staining.Results: Decorin, derived from decidual stromal cells, was highly expressed in the decidua of women with RPL.A positive correlation between decorin content and the proportion of M1-like macrophages was also observed in the decidua of early NP women.In vitro studies showed that decorin treatment inhibited macrophage polarization to M2-like subsets and boosted the inflammatory response, which was related to enhanced anaerobic glycolysis, increased mitochondrial membrane potential and intracellular reactive oxygen species levels, reduced mitochondrial mass, and activation of the myeloid differentiation primary response 88-nuclear factor-κB signaling pathway.Adoptive transfer of decorin-treated bone marrow-derived macrophages in pregnant C57BL/6 mice increased the embryo absorption, accompanied by impaired fetal vascularization.Conclusions: Decidual stromal cell-derived decorin can polarize decidual macrophages toward the M1 phenotype by regulating mitochondrial metabolism, resulting in the occurrence of RPL.
Association Between Consumption of Ultraprocessed Foods and Cognitive Decline
Authors: Natalia Gomes Gonçalves, Naomi Vidal Ferreira, Neha Khandpur, Euridice Martinez Steele, Renata Bertazzi Levy, Paulo Andrade Lotufo, Isabela M. Bensenor, Paulo Caramelli, Sheila Maria Alvim de Matos, Dirce M. Marchioni, Claudia Kimie Suemoto
Journal: JAMA Neurology (2022)

Although consumption of ultraprocessed food has been linked to higher risk of cardiovascular disease, metabolic syndrome, and obesity, little is known about the association of consumption of ultraprocessed foods with cognitive decline.To investigate the association between ultraprocessed food consumption and cognitive decline in the Brazilian Longitudinal Study of Adult Health.This was a multicenter, prospective cohort study with 3 waves, approximately 4 years apart, from 2008 to 2017. Data were analyzed from December 2021 to May 2022. Participants were public servants aged 35 to 74 years old recruited in 6 Brazilian cities. Participants who, at baseline, had incomplete food frequency questionnaire, cognitive, or covariate data were excluded. Participants who reported extreme calorie intake (<600 kcal/day or >6000 kcal/day) and those taking medication that could negatively interfere with cognitive performance were also excluded.Daily ultraprocessed food consumption as a percentage of total energy divided into quartiles.Changes in cognitive performance over time evaluated by the immediate and delayed word recall, word recognition, phonemic and semantic verbal fluency tests, and Trail-Making Test B version.A total of 15 105 individuals were recruited and 4330 were excluded, leaving 10 775 participants whose data were analyzed. The mean (SD) age at the baseline was 51.6 (8.9) years, 5880 participants (54.6%) were women, 5723 (53.1%) were White, and 6106 (56.6%) had at least a college degree. During a median (range) follow-up of 8 (6-10) years, individuals with ultraprocessed food consumption above the first quartile showed a 28% faster rate of global cognitive decline (β = -0.004; 95% CI, -0.006 to -0.001; P = .003) and a 25% faster rate of executive function decline (β = -0.003, 95% CI, -0.005 to 0.000; P = .01) compared with those in the first quartile.A higher percentage of daily energy consumption of ultraprocessed foods was associated with cognitive decline among adults from an ethnically diverse sample. These findings support current public health recommendations on limiting ultraprocessed food consumption because of their potential harm to cognitive function.
Hearing Aids and Cochlear Implants in the Prevention of Cognitive Decline and Dementia—Breaking Through the Silence
Authors: Michael W. Denham, Rachel E. Weitzman, Justin S. Golub
Journal: JAMA Neurology (2022)

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Effect of Wearing Glasses on Risk of Infection With SARS-CoV-2 in the Community
Authors: Atle Fretheim, Ingeborg Hess Elgersma, Arnfinn Helleve, Petter Elstrøm, Oliver Kacelnik, Lars G. Hemkens
Journal: JAMA Network Open (2022)

Importance Observational studies have reported an association between the use of eye protection and reduced risk of infection with SARS-CoV-2 and other respiratory viruses, but, as with most infection control measures, no randomized clinical trials have been conducted. Objectives To evaluate the effectiveness of wearing glasses in public as protection against being infected with SARS-CoV-2 and other respiratory viruses. Design, Setting, and Participants A randomized clinical trial was conducted in Norway from February 2 to April 24, 2022; all adult members of the public who did not regularly wear glasses, had no symptoms of COVID-19, and did not have COVID-19 in the last 6 weeks were eligible. Intervention Wearing glasses (eg, sunglasses) when close to others in public spaces for 2 weeks. Main Outcomes and Measures The primary outcome was a positive COVID-19 test result reported to the Norwegian Surveillance System for Communicable Diseases. Secondary outcomes included a positive COVID-19 test result and respiratory infection based on self-report. All analyses adhered to the intention-to-treat principle. Results A total of 3717 adults (2439 women [65.6%]; mean [SD] age, 46.9 [15.1] years) were randomized. All were identified and followed up in the registries, and 3231 (86.9%) responded to the end of study questionnaire. The proportions with a reported positive COVID-19 test result in the national registry were 3.7% (68 of 1852) in the intervention group and 3.5% (65 of 1865) in the control group (absolute risk difference, 0.2%; 95% CI, −1.0% to 1.4%; relative risk, 1.10; 95% CI, 0.75-1.50). The proportions with a positive COVID-19 test result based on self-report were 9.6% (177 of 1852) in the intervention group and 11.5% (214 of 1865) in the control group (absolute risk difference, –1.9%; 95% CI, −3.9% to 0.1%; relative risk, 0.83; 95% CI, 0.69-1.00). The risk of respiratory infections based on self-reported symptoms was lower in the intervention group (30.8% [571 of 1852]) than in the control group (34.1% [636 of 1865]; absolute risk difference, –3.3%; 95% CI, −6.3% to −0.3%; relative risk, 0.90; 95% CI, 0.82-0.99). Conclusions and Relevance In this randomized clinical trial, wearing glasses in the community was not protective regarding the primary outcome of a reported positive COVID-19 test. However, results were limited by a small sample size and other issues. Glasses may be worth considering as one component in infection control, pending further studies. Trial Registration ClinicalTrials.gov Identifier: NCT05217797
Vegetable, but Not Potato, Intake Is Associated With a Lower Risk of Type 2 Diabetes in the Danish Diet, Cancer and Health Cohort
Authors: Pratik Pokharel, Cecilie Kyrø, Anja Olsen, Anne Tjønneland, Kevin Murray, Lauren C. Blekkenhorst, Catherine P. Bondonno, Jonathan M. Hodgson, Nicola P. Bondonno
Journal: Diabetes Care (2022)

To examine the relationship between intake of vegetables/potatoes and incident type 2 diabetes (T2D) and explore whether the relationship between vegetable intake and incident T2D is mediated by baseline BMI.Cross-sectional associations between exposure (baseline intake of total vegetables, vegetable subgroups, and potatoes) and baseline BMI were assessed by multivariable-adjusted linear regression models. Associations between exposure and incident T2D were examined by multivariable-adjusted Cox proportional hazards models. Mediation by BMI was quantified through exploration of natural direct and indirect effects.Among 54,793 participants in the Danish Diet, Cancer and Health cohort, 7,695 cases of T2D were recorded during a median follow-up of 16.3 years. Participants in the highest total vegetable intake quintile (median 319 g/day) had a 0.35 kg/m2 (95% CI -0.46, -0.24) lower BMI and a 21% (95% CI 16, 26%) lower risk of incident T2D after multivariable adjustment compared with those in the lowest quintile (median 67 g/day). Baseline BMI mediated ∼21% of the association between vegetable intake and incident T2D. Participants in the highest compared with the lowest (median 256 vs. 52 g/day) potato intake quintile had a 9% (95% CI 2, 16%) higher risk of T2D after multivariable adjustment, with no association found after accounting for underlying dietary pattern. Of the vegetable subclasses, higher intake of green leafy and cruciferous vegetables was associated with a statistically significantly lower risk of T2D.The findings provide evidence that a higher vegetable, but not potato, intake might help mitigate T2D risk, partly by reducing BMI.
Identification of a miRNA-based non-invasive predictive biomarker of response to target therapy in BRAF-mutant melanoma
Authors: Ciro Francesco Ruggiero, Luigi Fattore, Irene Terrenato, Francesca Sperati, Valentina Salvati, Gabriele Madonna, Mariaelena Capone, Fabio Valenti, Simona Di Martino, Chiara Mandoj, Domenico Liguoro, Vittorio Castaldo, Giordana Cafaro, Ester Simeone, Vito Vanella, Michelangelo Russillo, Laura Conti, Giovanni Cuda, Diana Giannarelli, Paolo Antonio Ascierto, Rita Mancini, Gennaro Ciliberto
Journal: Theranostics (2022)

Rationale: Metastatic melanoma is the most aggressive and dangerous form of skin cancer.The introduction of immunotherapy with Immune checkpoint Inhibitors (ICI) and of targeted therapy with BRAF and MEK inhibitors for BRAF mutated melanoma, has greatly improved the clinical outcome of these patients.Nevertheless, response to therapy remains highly variable and the development of drug resistance continues to be a daunting challenge.Within this context there is a need to develop diagnostic tools capable of predicting response or resistance to therapy in order to select the best therapeutic approach.Over the years, accumulating evidence brought to light the role of microRNAs (miRNAs) as disease biomarkers.Methods: In particular, the detection of miRNAs in whole blood or specific blood components such as serum or plasma, allows these molecules to be good candidates for diagnosis, prognosis and for monitoring response to anticancer therapy.In this paper, we evaluated circulating basal levels of 6 previously identified miRNAs in serum samples of 70 BRAF-mutant melanoma patients before starting targeted therapy.Results: Results show that the circulating levels of the oncosuppressor miR-579-3p and of the oncomiR miR-4488 are able to predict progression free survival (PFS) but not overall survival (OS).Most importantly, we observed that the best predictor of disease outcome is represented by the ratio of circulating miR-4488 vs. miR-579-3p (miRatio).Finally, the combination of the Lactate dehydrogenase (LDH) blood levels with the two circulating miRNAs alone or together did not produce any improvement in predicting PFS indicating that miR-579-3p and miR-4488 are independent predictors of PFS as compared to LDH.Conclusions: All together these data underscored the relevance of circulating miRNAs as suitable tools to predict therapy response in melanoma and maybe further developed as companion diagnostics in the clinic.
TIMM44 is a potential therapeutic target of human glioma
Authors: Yi-zhuo Guo, Gang Chen, Man Huang, Yin Wang, Yuan-yuan Liu, Qin Jiang, Cong Cao, Fang Liu
Journal: Theranostics (2022)

TIMM44 (translocase of inner mitochondrial membrane 44) is essential for the maintenance of mitochondrial functions.Bioinformatics studies and results from the local high-grade glioma tissues showed that TIMM44 mRNA and protein levels are elevated in glioma, correlating with poor overall survival.Mitochondrial TIMM44 upregulation was also detected in patient-derived primary glioma cells and immortalized cell line.In primary and established glioma cells, TIMM44 depletion, using the lentiviral shRNA strategy or the CRISPR/Cas9 knockout (KO) method, robustly inhibited cell viability, proliferation and migration.Moreover, TIMM44 silencing/KO resulted in mitochondrial complex I inhibition, ATP depletion, mitochondrial membrane potential reduction, oxidative stress and DNA damage, and eventually provoked apoptosis.Conversely, ectopic overexpression of TIMM44 augmented glioma cell proliferation and migration.TIMM44 upregulation in glioma is possibly due to increased TIMM44 transcriptional machinery by the transcription factor GATA3 in a YME1L (YME1 Like 1 ATPase)-dependent manner.In vivo, the growth of subcutaneous glioma xenografts was suppressed after intratumoral injection of TIMM44 shRNA adeno-associated virus (AAV).TIMM44 depletion, ATP reduction, oxidative injury and apoptosis were detected in TIMM44 shRNA AAV-injected glioma xenografts.Moreover, the intracranial growth of TIMM44 KO glioma cells in the mouse brain was largely inhibited.Together, overexpressed TIMM44 could be a novel and promising therapeutic target of human glioma.
The current state of laboratory mycology and access to antifungal treatment in Europe: a European Confederation of Medical Mycology survey
Authors: Jon Salmanton-García, Martin Hoenigl, Jean-Pierre Gangneux, Esther Segal, Ana Alastruey-Izquierdo, Sevtap Arikan Akdagli, Katrien Lagrou, Volkan Özenci, Antonio Vena, Oliver A Cornely
Journal: The Lancet Microbe (2022)
Error in Table 1
Journal: JAMA Network Open (2022)

Jessica L. Gleason, PhD, MPH; Rajeshwari Sundaram, PhD; Susanna D. Mitro, PhD; Stefanie N. Hinkle, PhD; Stephen E. Gilman, ScD; Cuilin Zhang, MD, PhD; Roger B. Newman, MD; Kelly J. Hunt, MD; Daniel W. Skupski, MD; William A. Grobman, MD; Michael Nageotte, MD; Morgan Robinson, BS; Kurunthachalam Kannan, PhD; Katherine L. Grantz, MD, MS
Pharmacological Targeting of Androgen Receptor Elicits Context-Specific Effects in Estrogen Receptor–Positive Breast Cancer
Authors: Lixuan Wei, Huanyao Gao, Jia Yu, Huan Zhang, Thanh Thanh L. Nguyen, Yayun Gu, Marie R. Passow, Jodi M. Carter, Bo Qin, Judy C. Boughey, Matthew P. Goetz, Richard M. Weinshilboum, James N. Ingle, Liewei Wang
Journal: Cancer Research (2022)

Abstract Androgen receptor (AR) is expressed in 80% to 90% of estrogen receptor α–positive (ER+) breast cancers. Accumulated evidence has shown that AR is a tumor suppressor and that its expression is associated with improved prognosis in ER+ breast cancer. However, both a selective AR agonist (RAD140) and an AR inhibitor (enzalutamide, ENZ) have shown a therapeutic effect on ER+ breast cancer, so the potential for clinical application of AR-targeting therapy for ER+ breast cancer is still in dispute. In this study, we evaluated the efficacy of ENZ and RAD140 in vivo and in vitro in AR+/ER+ breast cancer models, characterizing the relationship of AR and ER levels to response to AR-targeting drugs and investigating the alterations of global gene expression and chromatin binding of AR and ERα after ENZ treatment. In the AR-low setting, ENZ directly functioned as an ERα antagonist. Cell growth inhibition by ENZ in breast cancer with low AR expression was independent of AR and instead dependent on ER. In AR-high breast cancer models, AR repressed ERα signaling and ENZ promoted ERα signaling by antagonizing AR. In contrast, RAD140 activated AR signaling and suppressed AR-high tumor growth by deregulating ERα expression and blocking ERα function. Overall, analysis of the dynamic efficacies and outcomes of AR agonist, and antagonist in the presence of different AR and ERα levels reveals regulators of response and supports the clinical investigation of ENZ in selected ER+ tumors with a low AR/ER ratio and AR agonists in tumors with a high AR/ER ratio. Significance: The ratio of androgen receptor to estrogen receptor in breast cancer dictates the response to AR-targeted therapies, providing guidelines for developing AR-directed treatment strategies for patients with breast cancer.
First-in-Maintenance Therapy for Localized High-Grade Osteosarcoma: An Open-Label Phase I/II Trial of the Anti–PD-L1 Antibody ZKAB001
Authors: Yan Zhou, Qingcheng Yang, Yang Dong, Tong Ji, Bing Zhang, Cheng Yang, Shuier Zheng, Lina Tang, Chenliang Zhou, Guowei Qian, Yujing Huang, Wenxi Yu, Hongtao Li, Yonggang Wang, Aina He, Zan Shen, Qiyuan Bao, Yingqi Hua, Hongyu Bai, Jiayi Zhao, Xiaoyi Li, Xiangrong Dai, Jianjun Zhang, Haiyan Hu, Yang Yao
Journal: Clinical Cancer Research (2022)

Abstract Purpose: We investigated the safety and preliminary efficacy of anti–PD-L1 antibody (ZKAB001) as maintenance therapy for localized patients with high-grade osteosarcoma to reduce the risk of recurrence and metastasis. Patients and Methods: This open-label Phase I/II study was divided into dose-escalation Phase I and expansion Phase II. Phase I used a 3+3 design with ZKAB001 at three escalating doses ranging: 5, 10, 15 mg/kg every 2 weeks in 9 patients with localized high-grade osteosarcoma and Phase II tested 10 mg/kg in 12 patients for up to 24 cycles. Primary endpoints were safety and tolerability assessed using CTCAE4.0.3. Results: Between October 2018 and 2019, 21 eligible patients were enrolled and accepted ZKAB001 treatment: 9 in the dose-escalation phase, and 12 in expansion phase. Six patients with disease progression withdrew from this study and follow-up is ongoing. The MTD was not defined in Phase I. All doses had a manageable safety profile. The recommended dose in Phase II was set at 10 mg/kg. Most frequent immune-related adverse events were thyroiditis (76.2%) and dermatitis (42.9%). Only 1 (4.8%) of 21 patients had a Grade 3 skin rash. The median 3-year event-free survival (EFS) and overall survival (OS) were not established; however, 24-month EFS was 71.4% (95% confidence interval, 47.2–86.0) and 2-year OS was 100%. Preliminary efficacy data showed EFS benefits in patients with PD-L1 positive or an MSI-H sub-population. Conclusions: Switching to maintenance using ZKAB001 showed an acceptable safety profile and provided preliminary evidence of clinical activity in localized patients with osteosarcoma.
Mutations in spliceosome genes in myelodysplastic neoplasms and their association to ring sideroblasts
Authors: Sandra Huber, Torsten Haferlach, Manja Meggendorfer, Stephan Hutter, Gregor Hoermann, Isolde Summerer, Irene Fuhrmann, Constance Baer, Wolfgang Kern, Claudia Haferlach
Journal: Leukemia (2022)
JAMA Internal Medicine
Authors: Thomas Easley, Brian Shields, Karen Adams-Taylor, Paul Gee, Anna Frazier, Monica Smith, Jeff Ery, J Bonistalli, Kathy Russell, Mirna Monal, Stacey Mchugh, Tim Melroy, Marketing Thornbury, Tricia Castellano, Meghan Coordinator, Sade Deramus-Townsend, Thalia Recruitment, Samantha Bauer, Hank Eurich, Marsha Fogler, Rachel Sisholtz, Saskia Bolore, Gretchen Linder, Brian Mccartney, Christine Hearne, Natasha Staff, Henry Aguillon, David Baum, Ron Marketing, Rick Bell, Elizabeth Solaro, Sara Zimmerman, Geoff Rey, Lindsay Dawson, Ellen Gibson, Craig Mccaff Rey, Michael Mcgraw, Daniel Pickhardt, Romando Rossini, Sarah Subramanian, Stacy Tucker, Walsh Business, Analyst Sirisha, Alluri Staff, Millette Jackson-Bates, Jacob Mishkin, Morgan Business, Lydia Cruz, Karl Elvin, Jaye Mize, Sean O'donnell, Joe Managers, David Antos, Anthony Bautista, Chris Borden, Debbie Camp, Scott Curl, Diane Darnell, Nanette Diaz, Jordynn Farrar, Sherry Flores, Allison Hughes, Colleen Kelly, John Lash, Chris Meyer, Tom Miller, Annemarie Neff, J Neff, Sean Ohlson, Phil O'leary, Bill Pedone, Susan Price, Jaynam Shah, Erin Spencer, Denise Steinhauser, Production Services, Ahmed Avendano, Kim Boler, Rhonda Brown, Fin Carter, Michael Deegan, Euwanaha Joiner-Smith, Joshua Lane, Cindy Rendlen, John Rhead, Janis Trinchere, Annissa Zak, Circulation Services, Julie Burton, Ronna Hewitt, Mary Sieck, Geneine Someren, Jamaal Vargas, Content Systems, Mike Bujewski, Nathan Mitre, Digital Production, Regina Brownlee, Amanda Camino, Brenda Chandler-Grayer, Emily Dunn, Amy Evers, Maleeka Holden, Teri Hutchison, Dan Knowles, Joshua Lampinen, Natalie Marsh, Patricia Panek, Marla Seidell, La Son Diggs-Sledge, Julian Graphics, Joe Amft, Jonathan Chala, Maria Duda, Fred Furtner, Carolyn Hall, Maria Kowalkowski, Proofreading Carol, Joy Farrell, Maria Giannini, Sasha Grossman, Kate Lander, Judith Literskis, Teresa Omiotek, Michael Ryder, James Madara, Terri Carter, Fellows Mithi, Del Rosario, Audrey Han, Isabel Ostrer, Natalie Richmond, Melinda Wang, Eric Ward, Grace Zhang, Zachary Goldberger, Nora Goldschlager, San Francisco, Elsayed Soliman, Winston-Salem North, Fiona Clement, Kirsten Bibbins-Domingo, Rita Redberg, Deborah Grady, Michael Incze, Salt City, Tanner Caverly, Ann Arbor, Brandon Combs, Sanket Dhruva
Journal: JAMA Internal Medicine (2022)

Mission Statement: To promote the art and science of medicine and the betterment of public health by publishing manuscripts of interest and relevance to internists practicing as generalists or as medical subspecialists.